Subjects with anterior cruciate ligament (ACL) injuries have a high risk of developing post-traumatic osteoarthritis (OA) despite ACL reconstruction. With the increasing number of ACL injuries in the adolescent population, we are poised to have an epidemic of young adults with post-traumatic OA and loss of function within the next decade. There is a profound need for early detection of biochemical and biomechanical abnormalities in ACL-injured and reconstructed knees. This ability to diagnose early degeneration will enable early intervention, and will provide guidance and critical evaluation for new surgical or pharmacological therapies. Magnetic resonance (MR) T{1p} and T{2} quantification have been used to detect early cartilage degeneration. However, no studies have yet investigated ACL-injured knees longitudinally using these advanced imaging techniques. Kinematic MRI allows for the determination of 3-D knee joint kinematics, including soft tissues, under specific loading conditions. Motion analysis provides evaluation of kinematics and kinetics of the entire limb during physiologic conditions such as walking, running and jumping. In this proposal, we will integrate these three quantitative measures, from tissue composition to joint kinematics and entire limb function, to longitudinally evaluate the biomechanical and biochemical abnormalities in ACL-injured and reconstructed knees. The central hypothesis is that abnormal kinematics and kinetics of ACL-injured and reconstructed knees, as measured by kinematic MRI and motion analysis, will lead to accelerated cartilage degeneration of the knee joint, as indicated by MRI T{1p} and T{2}. Specifically we aim to 1) investigate longitudinal changes in cartilage matrix in ACL-injured and reconstructed knees as indicated by MRI T{1p} and T{2};2) To investigate longitudinal changes in kinematics and kinetics in ACL-injured and reconstructed knees using kinematic MRI and motion analysis;and 3) To investigate interrelationship between knee cartilage degeneration and lower extremity kinematics and kinetics in ACL-injured knees. Bilateral knees of patients with acute ACL-injures will be studied at baseline (within 2-4 weeks post injury and prior to ACL reconstruction), 6-month, 1-year and 3-year post ACL reconstruction. Bilateral knees of age, gender and BMI-matched healthy subjects will be studied as controls. With our extensive experience in quantitative and kinematic MRI, and the availability of motion analysis within the Human Performance and Functional Testing Core, we are equipped to investigate the interaction between biochemical and biomechanical abnormalities of ACL-injured and reconstructed knees. A better understanding of this interaction is critical to advance our mechanistic knowledge of post-traumatic OA development in acutely-injured joints. Correlations between quantitative MRI and motion analysis will facilitate an understanding of the interactions leading to degeneration, and translating these techniques into the clinic will ultimately improve patient management and outcome.

Public Health Relevance

Patients with anterior cruciate ligament (ACL) ruptures tend to develop post-traumatic osteoarthritis despite ACL reconstruction. This proposal aims at evaluating the biochemical and biomechanical abnormalities in knees after ACL injuries and reconstruction using advanced MRI techniques and motion analysis. The study has the potential to improve management to patients with acute knee injures.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Specialized Center (P50)
Project #
5P50AR060752-03
Application #
8535527
Study Section
Special Emphasis Panel (ZAR1-KM)
Project Start
Project End
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
3
Fiscal Year
2013
Total Cost
$240,606
Indirect Cost
$46,759
Name
University of California San Francisco
Department
Type
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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